Predicted Heart Mass: A Tale of 2 Ventricles.

BACKGROUND: Total predicted heart mass (PHM) is the recommended metric to assess donor-recipient size matching in patients undergoing heart transplantation. Separately measuring right ventricular (RV) and left ventricular (LV) PHM may improve risk prediction of 1-year graft failure. METHODS: Adult heart transplant recipients from the UNOS database from 2000 to 2018 were included in the study. LV and RV PHM were modeled as restricted cubic splines. The association with 1-year graft failure was determined using adjusted Cox regression. The risk reclassification of using both LV and RV PHM versus total PHM was assessed using the net reclassification index. RESULTS: A total of 34 976 recipients were included. We observed a U-shaped association between total PHM and 1-year graft failure, such that risk increased for hearts undersized by >15% and those oversized by more than 27%. Graft failure incrementally increased when LV PHM was undersized by more than 5% and when RV was oversized by >20%. There was 1.5-fold greater risk of graft failure for an LV undersized by >26% or an RV oversized by more than 40%. Using LV and RV PHM risk-assessment separately led to a net reclassification index=8.5% ([95% CI, 5.3%-11.7%], nonevent net reclassification index=9.1%, event net reclassification index=-0.6%). CONCLUSIONS: The association between donor-recipient PHM match and the risk of graft failure after heart transplantation can be further understood as risk attributable to LV undersizing and RV oversizing. Assessing LV and RV PHM separately instead of total PHM could further refine the methods used to match donors and recipients for heart transplantation, minimize the risk of 1-year graft failure, and increase the use of donor organs.

Value of CT and 18F-FDG PET/CT Imaging for Preoperative Screening in Advanced Heart Failure Therapy Candidates.

This study assesses the impact of contrast-enhanced chest and abdominal computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in preoperative screening of heart transplantation or ventricular assist device candidates. Patients who underwent both studies within a 6-month interval at our institution between 2014 and 2021 were reviewed for significant findings, defined as possible contraindications or actionable findings. Among the 79 included patients, significant findings were found in 38 (48.1%) with CT and in 18 (22.8%) with FDG-PET/CT (P = 0.0015). FDG-PET/CT identified 10 additional significant findings, but none of these precluded patient listing for heart transplantation. Use of FDG-PET/CT may lead to unnecessary investigations when performed indiscriminately in all patients.

La présente étude se penche sur l'incidence du recours à une tomodensitométrie (TDM) thoracique et abdominale avec produit de contraste et à une tomographie par émission de positrons au fluorodésoxyglucose marqué au fluor 18 (TEP-18FDG) lors d'évaluation préopératoire de candidats à une transplantation cardiaque ou à l'implantation d'un dispositif d'assistance ventriculaire. Les résultats obtenus de 79 patients qui ont subi ces deux examens dans un intervalle maximal de six mois à notre établissement entre 2014 et 2021 ont été analysés à la recherche de conclusions pertinentes, définies comme des contre-indications possibles à l'intervention ou des résultats ayant un impact direct sur la prise en charge du patient. De telles conclusions ont été constatées chez 38 participants (48,1 %) suite à une TDM et 18 participants (22,8 %) suite à une TEP-18FDG (p = 0,0015). La TEP-18FDG a permis de relever 10 résultats d'importance supplémentaires, mais aucun d'entre eux n'aurait entraîné l'inadmissibilité du patient à une transplantation cardiaque. L'utilisation de la TEP-18FDG pourrait donner lieu à des examens non nécessaires lorsqu'elle est réalisée sans distinction chez tous les patients.

FDG-PET/CT and rest myocardial perfusion imaging to predict high-degree atrioventricular block recovery in cardiac sarcoidosis.

BACKGROUNDS: High-degree atrioventricular block (AVB) recovery in CS has been shown to be highly variable despite immunosuppressive treatment, with no reliable tool available to predict odds of reversibility. This study sought to evaluate the potential of combined fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and resting myocardial perfusion imaging (rMPI) to predict reversibility of newly diagnosed high-grade AVB in cardiac sarcoidosis (CS). METHODS: We performed a single-center, retrospective analysis of patients with CS presenting with high-grade AVB who underwent combined FDG-PET/CT and rMPI. The 2016 JCS and the 2014 HRS diagnostic criteria were used for the diagnosis of CS. Patients with a history of coronary artery disease or prior immunosuppressive treatment were excluded. Patients were divided into AVB recovery and non-recovery subgroups. CS disease staging was based on FDG-PET and rMPI findings: (Stage 0) normal FDG-PET and rMPI (Stage 1) positive FDG-PET and normal rMPI (Stage 2) positive FDG-PET with perfusion deficits on rMPI (Stage 3) normal FDG-PET with perfusion deficits on rMPI. RESULTS: Twenty-seven patients, including 13 demonstrating AVB recovery, were identified. Eleven out of fourteen (78.6%) patients presenting with stage 1 CS demonstrated AVB recovery. Stage 1 CS was significantly more present in the recovery group compared to the non-recovery group (84.6% vs 21.4%, P = .002). Eleven presented with stage 2 CS, with only 2 (18.2%) recovering AV nodal conduction. Stage 2 CS presented more frequently in the non-recovery group (64.3% vs 15.4%, P = .020). CONCLUSIONS: Combined FDG-PET and rMPI employed to stage CS disease presenting with high-degree AVB appears to have good performance for predicting likelihood of recovery.

Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) associated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants cause HCM. Mendelian randomization analyses support a causal role of increased LV contractility in both obstructive and non-obstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, the findings significantly increase our understanding of the genetic basis and molecular mechanisms of HCM, with potential implications for disease management.

Intrinsic Atrial Myopathy Precedes Left Ventricular Dysfunction and Predicts Atrial Fibrillation in Lamin A/C Cardiomyopathy.

BACKGROUND: In Lamin A/C (LMNA) cardiomyopathy, atrial fibrillation (AF) commonly occurs before dilated cardiomyopathy, and the ability to predict its incidence is limited. We hypothesized that left atrial (LA) echocardiographic phenotyping can identify atrial myopathy and harbingers of AF. METHODS: Echocardiograms from patients with pathogenic or likely pathogenic variants in LMNA (n=77) with and without reduced left ventricular ejection fraction (LVEF, <50%) were compared to healthy individuals (n=70) and patients with Titin truncating variant cardiomyopathy (TTNtv) (n=35) with similar LVEF, sex, and age distributions. Echocardiographic analysis, blinded to genotype, included strain and volumetric measures of left ventricular and atrial function. The primary outcome was incident AF. RESULTS: At baseline, 43% of the patients with pathogenic or likely pathogenic LMNA variants had a history of AF, including 26% of those with LVEF ≥50%. Compared with healthy subjects, the patients with pathogenic or likely pathogenic LMNA variants and LVEF ≥50% had reduced LA contractile strain (LMNA, 11.8±6.1% versus control, 15.0±4.2%; P=0.003). Compared to LVEF-matched (TTNtv) patients, the patients with pathogenic or likely pathogenic LMNA variants and LVEF <50% displayed no difference in LA size, but a worse LA contractile dysfunction (6.4±4.7% versus 12.6±9.6%; P=0.02). Over a median follow-up of 2.8 (1.2-5.7) years, LA contractile strain was the only significant predictor of AF in multivariable Cox regression (hazard ratio, 4.0 [95% CI, 1.04-15.2]). CONCLUSIONS: LMNA cardiomyopathy is associated with early intrinsic atrial myopathy reflected by high AF prevalence and reduced LA contractile strain, even in the absence of LV dysfunction and LA dilation. Whether LA strain can be used as a monitoring strategy to detect and mitigate AF complications requires validation.

Contemporary Management of Cardiogenic Shock During Pregnancy.

Cardiogenic shock is the most extreme cardiovascular disease state during pregnancy. Peripartum cardiomyopathy is the most common cause of cardiogenic shock toward the end of pregnancy and in the early postpartum period. Therapy for cardiogenic shock relies on appropriate phenotyping of shock etiology, severity and ventricular predominance, which are critical in the appropriate selection of medical and mechanical therapy. Mechanical circulatory support may be used as a bridge to recovery or as definitive therapy. Intra-aortic balloon pumps, percutaneous left ventricular assist devices and venoarterial extracorporeal circulatory devices have been successfully used in pregnancy and the postpartum period. The most commonly used mechanical therapy in the pregnant patient is extracorporeal membranous oxygenation circulatory support. The use of mechanical circulatory devices in peripartum cardiomyopathy has contributed to improved survival rates in recent years. Further efforts to identify the optimal mechanical circulatory support strategy for peripartum cardiomyopathy and cardiogenic shock in the peripartum period are needed.

Optimization of pharmacotherapies for ambulatory patients with heart failure and reduced ejection fraction is associated with improved outcomes.

BACKGROUND: In heart failure, specific target doses for each drug are recommended, but some patients receive suboptimal dosing, others are undertreated or remain chronically in a titration phase, despite having no apparent contraindication or intolerance. We assessed the association of different levels of adherence to guidelines with outcomes in patients with heart failure and reduced ejection fraction (HFrEF). METHODS: Medical records of patients with HFrEF followed at our heart failure (HF) clinic for at least 6 months (n = 511) were reviewed and patients categorized as: 1) optimized (25.4%); 2) in-titration (29.0%); 3) undertreated (32.7%); and 4) intolerant/contraindicated (12.9%). Risk of mortality or HF events (hospitalization, emergency visit or ambulatory administration of intravenous diuretics) within one year was assessed using Cox regression models and Kaplan-Meier curves. RESULTS: Compared to optimized patients, those intolerant (HR: 4.60 [95%CI: 2.23-9.48]; p < 0.0001) had the highest risk of outcomes, followed by those undertreated (3.45 [1.78-6.67]; p = 0.0002) and in-titration (1.99 [0.97-4.06]; p = 0.0588). Overall predictors of outcomes included loop diuretics' use (4.54 [2.39-8.60]), undertreatment (2.38 [1.22-4.67]), intolerance/ contraindication to triple therapy (3.08 [1.47-6.42]), peripheral vascular disease (2.13 [1.29-3.50]) and NYHA class III-IV (1.89 [1.25-2.85]); all p < 0.05. CONCLUSION: Level of adherence to guidelines is associated with outcomes, with intolerant/contraindicated patients having the worst prognosis and those undertreated and in-titration at intermediate risk compared to those optimized. Up-titration of therapy should be attempted whenever possible, considering patients' limitations, to potentially improve outcomes.

Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.

Aim: To investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years. Methods: Patients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test. Results: The prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively). Conclusion: Over 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.

Association Between Right Ventricular Dysfunction and Adverse Outcomes in Peripartum Cardiomyopathy: Insights From the BRO-HF Quebec Cohort Study.

Background: Peripartum cardiomyopathy (PPCM) is associated with severe morbidity and mortality, and the significance of right ventricular (RV) involvement is unclear. We sought to determine whether RV systolic dysfunction or dilatation is associated with adverse clinical outcomes in women with PPCM. Methods: We conducted a multicentre retrospective cohort study examining the association between echocardiographic RV systolic dysfunction or dilatation at the time of PPCM diagnosis and clinical outcomes. Clinical endpoints of interest were the need for mechanical support, recovery of left ventricular ejection fraction at follow-up, and a combined endpoint of hospitalization for heart failure, cardiac transplant, or death. Results: A total of 67 women, median age 30 years (interquartile range: 7), were diagnosed with PPCM between 1994 and 2015 in 17 participating centres. Twin pregnancies occurred in 11%; 62% of women were multiparous; and 24% had preeclampsia. RV systolic function was impaired in 18 (27%) and dilated in 8 (12%). Seven women required ventricular assistance, and 8 experienced the composite outcome during follow-up (25 [interquartile range 61] months). RV dysfunction was associated with the need for mechanical support (odds ratio 10.10 (95% confidence interval: 1.86-54.81), P = 0.007), but neither RV dysfunction nor dilatation was associated with left ventricular ejection fraction recovery, the need for cardiac transplant, heart failure hospitalization, or death. Conclusions: RV dysfunction is associated with the need for mechanical support in women with PPCM. These findings may improve risk stratification of complications and clinical management.

Introduction: La cardiomyopathie du péripartum (CMP-PP) est associée à la morbidité grave et à la mortalité, mais on ignore l'importance de l'atteinte ventriculaire droite (VD). Nous avons cherché à déterminer si la dysfonction systolique ou la dilatation VD sont associées aux résultats cliniques défavorables chez les femmes atteintes de CMP-PP. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique sur l'association entre la dysfonction systolique ou la dilatation VD à l'échographie au moment du diagnostic de CMP-PP et les résultats cliniques. Les critères cliniques d'intérêt étaient la nécessité d'une assistance mécanique, la récupération de la fraction d'éjection ventriculaire gauche (FEVG) au suivi et un critère combiné d'hospitalisation liée à l'insuffisance cardiaque (IC), la transplantation cardiaque ou la mort. Résultats: Un total de 67 femmes, dont l'âge médian était de 30 ans (écart interquartile [EI] : 7), ont reçu un diagnostic de CMP-PP entre 1994 et 2015 dans 17 centres participants. Les grossesses gémellaires sont survenues chez 11 % ; 62 % de femmes étaient multipares ; et 24 % souffraient de prééclampsie. La fonction systolique VD était compromise chez 18 (27 %) femmes et le VD, dilaté, chez huit (12 %) femmes. Sept femmes ont eu besoin d'une assistance ventriculaire, et huit ont subi le critère composite durant le suivi (25 [EI : 61] mois). La dysfonction VD a été associée à la nécessité d'une assistance mécanique (rapport de cotes 10,10 [intervalle de confiance à 95 % : 1,86-54,81], P = 0,007), mais ni la dysfonction ni la dilatation VD n'ont été associées à la récupération de la FEVG, à la nécessité d'une transplantation cardiaque, à une hospitalisation liée à l'IC ou à la mort. Conclusions: La dysfonction VD est associée à la nécessité d'une assistance mécanique chez les femmes atteintes de CMP-PP. Ces conclusions peuvent permettre d'améliorer la stratification des risques de complications et la prise en charge clinique.

Arrhythmic Sudden Cardiac Death in Heart Failure With Preserved Ejection Fraction: Mechanisms, Genetics, and Future Directions.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly recognized disorder. Many clinical trials have failed to demonstrate benefit in patients with HFpEF but have recognized alarming rates of sudden cardiac death (SCD). Genetic testing has become standard in the workup of patients with otherwise unexplained cardiac arrest, but the genetic architecture of HFpEF, and the overlap of a genetic predisposition to HFpEF and arrhythmias, is poorly understood. An understanding of the genetics of HFpEF and related SCD has the potential to redefine and generate novel diagnostic, prognostic, and therapeutic tools. In this review, we examine recent pathophysiological and clinical advancements in our understanding of HFpEF, which reinforce the heterogeneity of the condition. We also discuss data describing SCD events in patients with HFpEF and review the current literature on genetic underpinnings of HFpEF. Mechanisms of arrhythmogenesis which may lead to SCD in this population are also explored. Lastly, we outline several areas of promise for experimentation and clinical trials that have the potential to further advance our understanding of and contribute to improved clinical care of this patient population.

L'insuffisance cardiaque à fraction d'éjection préservée (ICFEP) est une anomalie de plus en plus reconnue. De nombreux essais cliniques n'ont pas permis de démontrer les avantages chez les patients atteints d'ICFEP, mais ont permis de reconnaître les taux alarmants de mort subite d'origine cardiaque (MSC). Le dépistage génétique est désormais un examen qui fait partie du bilan de santé des patients qui subissent un arrêt cardiaque inexpliqué autrement, mais l'architecture génétique de l'ICFEP et le chevauchement entre la prédisposition génétique à l'ICFEP et la prédisposition aux arythmies demeurent mal compris. La compréhension de la génétique de l'ICFEP et de la MSC associée a le potentiel de redéfinir et de générer de nouveaux outils de diagnostic, de pronostic et de traitement. Dans la présente revue, nous nous sommes penchés sur les récentes avancées physiopathologiques et cliniques dans notre compréhension de l'ICFEP, qui renforcent l'hétérogénéité de cette maladie. Nous nous sommes aussi intéressés aux données qui décrivent les événements de MSC chez les patients atteints d'ICFEP et passons en revue la littérature actuelle sur les fondements génétiques de l'ICFEP. Les mécanismes de l'arythmogenèse qui peuvent mener à la MSC au sein de cette population sont aussi abordés. Enfin, nous présentons plusieurs domaines d'expérimentation prometteurs et les essais cliniques qui ont le potentiel de faire progresser notre compréhension et de contribuer à l'amélioration des soins cliniques au sein de cette population de patients.

Sleep apnea and the risk of dementia: A systematic review and meta-analysis.

Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

AIMS: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. METHODS AND RESULTS: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3 year estimated median difference in event-free survival in those who responded to CRT (p = 0.04). CONCLUSION: Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.

Long-Chain Acylcarnitines and Monounsaturated Fatty Acids Discriminate Heart Failure Patients According to Pulmonary Hypertension Status.

Defects in fatty acid (FA) utilization have been well described in group 1 pulmonary hypertension (PH) and in heart failure (HF), yet poorly studied in group 2 PH. This study was to assess whether the metabolomic profile of patients with pulmonary hypertension (PH) due HF, classified as group 2 PH, differs from those without PH. We conducted a proof-of-principle cross-sectional analysis of 60 patients with chronic HF with reduced ejection fraction and 72 healthy controls in which the circulating level of 71 energy-related metabolites was measured using various methods. Echocardiography was used to classify HF patients as noPH-HF (n = 27; mean pulmonary artery pressure [mPAP] 21 mmHg) and PH-HF (n = 33; mPAP 35 mmHg). The profile of circulating metabolites among groups was compared using principal component analysis (PCA), analysis of covariance (ANCOVA), and Pearson's correlation tests. Patients with noPH-HF and PH-HF were aged 64 ± 11 and 68 ± 10 years, respectively, with baseline left ventricular ejection fractions of 27 ± 7% and 26 ± 7%. Principal component analysis segregated groups, more markedly for PH-HF, with long-chain acylcarnitines, acetylcarnitine, and monounsaturated FA carrying the highest loading scores. After adjustment for age, sex, kidney function, insulin resistance, and N-terminal pro-brain natriuretic peptide (NT-proBNP), 5/15 and 8/15 lipid-related metabolite levels were significantly different from controls in noPH-HF and PH-HF subjects, respectively. All metabolites for which circulating levels interacted between group and NT-proBNP significantly correlated with NT-proBNP in HF-PH, but none with HF-noPH. FA-related metabolites were differently affected in HF with or without PH, and may convey adverse outcomes given their distinct correlation with NT-proBNP in the setting of PH.

Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). METHODS: Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. RESULTS: Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001). CONCLUSION: In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.

Recent Trends of Infectious Complications Following Heart Transplantation.

BACKGROUND: Heart transplantation is a life-saving procedure that has seen improvements in transplant and patient outcomes due to advances in immunosuppression and prevention of posttransplantation infectious episodes (IEps). This study systematically evaluates IEps in the modern era of heart transplantation at Stanford University Medical Center. METHODS: This is a single-center retrospective review that includes 279 consecutive adult heart transplantation recipients from January 2008 to September 2017. Baseline demographic, clinical, serological, and outcomes information were collected. Kaplan-Meier estimator was used to assess survival stratified by IEp occurrence within the first year. RESULTS: A total of 600 IEps occurred in 279 patients (2.15 IEps per patient) during a median follow-up period of 3 years. Overall survival was 83.3% (95% confidence interval [CI], 76.2-88.4) at 1 year posttransplantation for those with any IEp compared with 93.0% (95% CI, 87.2-96.4) in those without IEp (P = 0.07). Bacterial IEps were the most common (n = 375; 62.5%), followed by viral (n = 180; 30.0%), fungal (n = 40; 6.7%), and parasitic (n = 5; 0.8%). IEps by Gram-negative bacteria (n = 210) outnumbered those by Gram-positive bacteria (n = 142). Compared with prior studies from our center, there was a decreased proportion of viral (including cytomegalovirus), fungal (including Aspergillus spp. and non-Aspergillus spp. molds), and Nocardia infections. There were no IEps due to Mycobacterium tuberculosis, Pneumocystis jirovecii, or Toxoplasma gondii. CONCLUSIONS: A significant reduction in viral, fungal, and Nocardia IEps after heart transplantation was observed, most likely due to advancements in immunosuppression and preventive strategies, including pretransplant infectious diseases screening and antimicrobial prophylaxis.

Outcomes of patients with infection related to a ventricular assist device after heart transplantation.

BACKGROUND: Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. METHODS: Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. RESULTS: Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. CONCLUSIONS: Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of -13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17-2.08]) and RVSP (1.37 [1.09-1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.

Gene expression profiling and racial disparities in outcomes after heart transplantation.

BACKGROUND: African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry. METHODS: Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx. The Kaplan-Meier method with delayed entry was used to describe differences in outcomes. Multivariable Cox hazard regression was used to evaluate the associations of overall gene expression profiling score, MARCH8 and FLT3 expression, and tacrolimus levels with each outcome, and stratified Cox models were developed to quantify race-specific associations. RESULTS: Among 933 eligible recipients, 737 (79%) were Caucasian and 196 (21%) were AA. Compared with Caucasians, AAs were significantly younger (55 vs 59 years, p < 0.001), with higher rates of non-ischemic cardiomyopathy (68% vs 50%, p < 0.001), sensitization (>10% panel reactive antibody, 16% vs 9.1%, p = 0.009), and human leukocyte antigen mismatches (7 vs 7, p = 0.01), but less frequent primary cytomegalovirus serostatus mismatch (14.31% vs 27.3%, p < 0.001). Overall, AAs had an increased adjusted mortality risk (hazard ratio [HR] 4.13, p = 0.007). Higher tacrolimus levels were associated with decreased mortality in AAs (HR 0.62, p = 0.009). Overall gene expression profiling score was associated with increased mortality among Caucasians (HR 1.21, p = 0.048). In Caucasians, but not AAs, overexpression of MARCH8 was associated with increased mortality (HR 2.90, p = 0.001). FLT3 upregulation was associated with increased mortality (HR 2.42, p = 0.033) in AAs. There was an inverse relationship between FLT3 expression and tacrolimus levels (-0.029 and -0.176, respectively) in Caucasians and AAs. CONCLUSIONS: AAs have a significantly higher mortality risk after HTx than Caucasians, even in the low-risk Outcomes AlloMap Registry population. AAs and Caucasians had differential outcomes based upon the varying expression of MARCH8 and FLT3 genes following HTx.